Evidence map›Paper›PMID 36669483›Full record

ArticleCell2023

Opioid-induced fragile-like regulatory T cells contribute to withdrawal.

Yongsheng Zhu, Peng Yan, Rui Wang, Jianghua Lai, Hua Tang, Xu Xiao, Rongshan Yu, Xiaorui Bao, Feng Zhu, Kena Wang and 13 more

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 1 pooled it
7.7field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

44 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.

  1. Pooled it
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  8. Regulatory T cells in cancer and inflammation.Signal transduction and targeted therapy · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 6 institutions in 1 country.

Yongsheng ZhuNational Biosafety Evidence Foundation, Bio-evidence Sciences Academy, Western China Science and Technology Innovation Harbor, Xi'an Jiaotong University, Xi'an, Shaanxi 710115, China.
Peng YanNational Biosafety Evidence Foundation, Bio-evidence Sciences Academy, Western China Science and Technology Innovation Harbor, Xi'an Jiaotong University, Xi'an, Shaanxi 710115, China.
Rui WangFujian Provincial Key Laboratory of Organ and Tissue Regeneration, Xiamen Key Laboratory of Regeneration Medicine, Organ Transplantation Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China; National Institute for Data Science in Health and Medicine, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China; School of Informatics, Xiamen University, Xiamen, Fujian 361005, China.
Jianghua LaiNational Biosafety Evidence Foundation, Bio-evidence Sciences Academy, Western China Science and Technology Innovation Harbor, Xi'an Jiaotong University, Xi'an, Shaanxi 710115, China.
Hua TangXi'an International Medical Center Hospital, Xi'an, Shaanxi 710117, China.
Xu XiaoNational Institute for Data Science in Health and Medicine, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China; School of Informatics, Xiamen University, Xiamen, Fujian 361005, China.
Rongshan YuNational Institute for Data Science in Health and Medicine, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China; School of Informatics, Xiamen University, Xiamen, Fujian 361005, China.
Xiaorui BaoFujian Provincial Key Laboratory of Organ and Tissue Regeneration, Xiamen Key Laboratory of Regeneration Medicine, Organ Transplantation Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China; National Institute for Data Science in Health and Medicine, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China.
Feng ZhuCenter for Translational Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
Kena WangNational Biosafety Evidence Foundation, Bio-evidence Sciences Academy, Western China Science and Technology Innovation Harbor, Xi'an Jiaotong University, Xi'an, Shaanxi 710115, China.
Ye LuNational Biosafety Evidence Foundation, Bio-evidence Sciences Academy, Western China Science and Technology Innovation Harbor, Xi'an Jiaotong University, Xi'an, Shaanxi 710115, China.
Jie DangSchool of Basic Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, China.
Chao ZhuDepartment of Nephrology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
Rui ZhangDepartment of Emergency Medicine, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China.
Wei DangThe Sixth Ward, Xi'an Mental Health Center, Xi'an, Shannxi 710100, China.
Bao ZhangNational Biosafety Evidence Foundation, Bio-evidence Sciences Academy, Western China Science and Technology Innovation Harbor, Xi'an Jiaotong University, Xi'an, Shaanxi 710115, China.
Quanze FuFujian Provincial Key Laboratory of Organ and Tissue Regeneration, Xiamen Key Laboratory of Regeneration Medicine, Organ Transplantation Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China; National Institute for Data Science in Health and Medicine, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China.
Qian ZhangFujian Provincial Key Laboratory of Organ and Tissue Regeneration, Xiamen Key Laboratory of Regeneration Medicine, Organ Transplantation Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China; National Institute for Data Science in Health and Medicine, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China.
Chongao KangFujian Provincial Key Laboratory of Organ and Tissue Regeneration, Xiamen Key Laboratory of Regeneration Medicine, Organ Transplantation Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China; National Institute for Data Science in Health and Medicine, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China.
Yujie ChenFujian Provincial Key Laboratory of Organ and Tissue Regeneration, Xiamen Key Laboratory of Regeneration Medicine, Organ Transplantation Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China; National Institute for Data Science in Health and Medicine, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China.
Xiaoyu ChenFujian Provincial Key Laboratory of Organ and Tissue Regeneration, Xiamen Key Laboratory of Regeneration Medicine, Organ Transplantation Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China; National Institute for Data Science in Health and Medicine, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China.
Qing LiangFujian Provincial Key Laboratory of Organ and Tissue Regeneration, Xiamen Key Laboratory of Regeneration Medicine, Organ Transplantation Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China; National Institute for Data Science in Health and Medicine, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China. Electronic address: liangqing@xmu.edu.cn.
Kejia WangFujian Provincial Key Laboratory of Organ and Tissue Regeneration, Xiamen Key Laboratory of Regeneration Medicine, Organ Transplantation Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China; National Institute for Data Science in Health and Medicine, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China. Electronic address: wangkejia@xmu.edu.cn.
Xiamen University · CNXi'an Jiaotong University · CNSecond Military Medical University · CNFirst Affiliated Hospital of Xi'an Jiaotong University · CNNingxia Medical University · CNXian Mental Health Center · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dysregulation of the immune system is a cardinal feature of opioid addiction. Here, we characterize the landscape of peripheral immune cells from patients with opioid use disorder and from healthy controls. Opioid-associated blood exhibited an abnormal distribution of immune cells characterized by a significant expansion of fragile-like regulatory T cells (Tregs), which was positively correlated with the withdrawal score. Analogously, opioid-treated mice also showed enhanced Treg-derived interferon-γ (IFN-γ) expression. IFN-γ signaling reshaped synaptic morphology in nucleus accumbens (NAc) neurons, modulating subsequent withdrawal symptoms. We demonstrate that opioids increase the expression of neuron-derived C-C motif chemokine ligand 2 (Ccl2) and disrupted blood-brain barrier (BBB) integrity through the downregulation of astrocyte-derived fatty-acid-binding protein 7 (Fabp7), which both triggered peripheral Treg infiltration into NAc. Our study demonstrates that opioids drive the expansion of fragile-like Tregs and favor peripheral Treg diapedesis across the BBB, which leads to IFN-γ-mediated synaptic instability and subsequent withdrawal symptoms.

Indexed as

Interferon-gammaOpioid-Related DisordersSubstance Withdrawal SyndromeT-Lymphocytes, RegulatoryAnalgesics, OpioidAnimalsMiceAnalgesics, OpioidInterferon-gammainterferon-γopioidregulatory T cellsynaptic plasticitywithdrawal symptom

Identifiers

PMID36669483
OpenAlexW4317435345

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.